This study has aimed to characterize, understand the pathogenesis of, and better manage severe life-threatening chronic infections with Epstein-Barr virus (EBV). To date, we have studied over 18 patients, many of whom have already succumbed to the disorder and its complications. We have developed tools to define and quantitate the presence of EBV in various patient tissues and blood and measured overall immune competence of the patients. This past year we realized that the long-spending therapeutic approach we used for 20 years, namely, the use of immunosuppressive drugs, afforded considerable but only transient benefit. We concluded that a more aggressive treatment strategy is required and we referred our first patient for bone marrow transplant, which appears successful. We also sought evidence in our patients this year for mutations in the SAP gene associated with the development of a different spectrum of EBV disease known as the X-linked lymphoproliferative syndrome. None of the 5 boys or 2 girls in our study group were found to harbor these mutations.